Spaarne Gasthuis

Malignant and non-malignant cells within the tumor microenvironment (TME) actively secrete extracellular vesicles (EVs) that may mediate intercellular communication or enter the blood stream. Circulating EVs in Diffuse Large B-Cell Lymphoma (DLBCL) patients are a promising source of liquid biopsy biomarkers; however, whether different cellular components of the TME preferentially secrete small (S-) and/or large (L-) EVs is still unknown. With an established density-gradient separation protocol and tunable resistive pulse sensing analysis, we demonstrate that DLBCL cells in culture produce 100-1000-fold higher numbers of S-EVs (50-200nm) compared with L-EVs (200-1000nm) and very large EVs (>1000nm). In contrast, the plasma from DLBCL patients contains comparable concentrations of S- and L-EVs, consistent with various cellular origins. Small RNA sequencing showed minor differences in miRNA content between plasma S- and L-EVs; however, messenger RNA sequencing revealed stark differences in cargo between EV-size subtypes and between healthy donors and patients. Deconvolution analysis with single-cell sequencing data from 17 DLBCL tumor tissues as reference using the Statescope algorithm indicated that circulating S-EVs from malignant cells outnumber the L-EVs. In contrast, TME macrophage-, T cell-, and natural killer-derived L-EVs outnumber S-EVs. Together, these findings suggest that circulating S- and L-EVs can originate from distinct cellular compartments within the DLBCL TME, representing complementary biological information. These observations have important implications for the development of EV-based liquid biopsy strategies.

Patients with an osteochondral lesion of the talus (OLT) often present with deep ankle pain, but the direct relationship between structural damage and the perceived pain remains unclear. The aim of this study was therefore to determine whether pain is associated with demographic and radiologic (computed tomography [CT]-only) lesion characteristics. This cross-sectional study was conducted in patients with symptomatic OLTs at a tertiary referral academic hospital. The primary outcome was the Pain subscale of the Foot and Ankle Outcome Score (FAOS). Secondary outcomes included the Numeric Rating Scale (NRS) for pain at rest and during walking, as well as the other FAOS subscales. Associations with patient demographics, lesion size, morphology, and location were assessed using univariate linear regression, followed by multivariate linear regression with backward selection. A total of 310 patients were included. In the final multivariate model for the FAOS Pain subscale, higher age (β = -0.18, P = .04) and smoking (β = -8.70, P < .001) were significantly associated with worse pain scores. Lesion morphology characterized by the presence of an osteochondral fragment was associated with lower NRS pain scores during walking. For NRS pain at rest, worse scores were significantly associated with female sex, higher body mass index, smoking, non-primary lesion nature, and greater lesion depth. No association was found between CT-based radiologic lesion characteristics and patient-reported pain as measured by the FAOS Pain subscale. In secondary analyses, some lesion characteristics showed associations, but these were limited and directionally inconsistent. These findings suggest structural damage alone does not seem to fully explain the patient's pain. Given the CT‑only approach and other design constraints, further research is warranted.

The current EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines recommend radiolabeled prostate-specific membrane antigen (PSMA), choline, or fluciclovine PET/CT at biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy. While studies compared [68Ga]Ga-PSMA-11 and [18F]Fluciclovine, data on 18F-labelled PSMA-ligands versus [18F]Fluciclovine in patients with low prostate-specific antigen (PSA) levels (< 2 ng/mL) are limited. This study compared the detection rates of [18F]Fluciclovine and [18F]DCFPyL PET/CT in patients with BCR after robot-assisted radical prostatectomy (RARP). Secondary objectives included stratifying detection rates by PSA level, anatomical regions and assessing inter-observer agreement. In this prospective, single-center study, patients with BCR (PSA 0.2-2.0 ng/mL) underwent both [18F]Fluciclovine and [18F]DCFPyL PET/CT within 15 days. Three blinded nuclear medicine experts independently reviewed all scans. Lesions were classified as positive or negative in predefined regions (i.e., prostate bed, pelvic and extra-pelvic lymph nodes, bone, and visceral). Discrepancies were resolved by consensus, defined as majority agreement (≥ 2/3 readers). Inter-observer agreement was assessed using Fleiss’ kappa. Overall scan positivity was 44% (22/50 patients) for [18F]DCFPyL PET/CT and 24% (12/50) for [18F]Fluciclovine PET/CT (p = 0.018). Detection rates increased with rising PSA levels for both tracers. Local recurrence was detected by both tracers in 16% (8/50) of patients. Metastatic disease detection rates for [18F]DCFPyL versus [18F]Fluciclovine were 22% vs. 8.0% for pelvic lymph nodes (p = 0.016), and 6.0% versus 2.0% for distant metastases (p = 0.50), respectively. Inter-observer agreement was moderate for both tracers (κ = 0.59 for [18F]DCFPyL and κ = 0.55 for [18F]Fluciclovine). This study demonstrated the superiority of [18F]DCFPyL over [18F]Fluciclovine in detecting pelvic lymph node metastases in patients presenting with BCR after RARP at low PSA levels. These findings suggest the potential of [18F]DCFPyL PET/CT to facilitate earlier and more personalized salvage treatment strategies.

IntroductionThe Latarjet procedure is the mainstay treatment in high-demand patients with substantial glenoid bone loss or after failed capsulolabral repairs. Patients typically return to sport (RTS) within 6 months postoperatively, requiring intensive rehabilitation. Current rehabilitation protocols focus on mobility, strength and stability. Yet, psychological factors, such as fear of reinjury, are the main reason not to RTS. Therefore, this study aims to determine whether integrating psychological interventions into postoperative rehabilitation improves patient-reported shoulder function compared with physical therapy alone.Methods and analysisThis monocentric randomised controlled trial will enrol 52 patients undergoing a Latarjet procedure for anterior shoulder instability. Participants will be equally and randomly assigned to either postoperative physical therapy combined with cognitive behavioural therapy or physical therapy alone. Eligibility criteria include patients aged 18–67 years undergoing an open or arthroscopic Latarjet procedure at our institution. Exclusion criteria include posterior or multidirectional instability, rotator cuff tear, prior shoulder surgery, anxiety disorder, using anxiolytics, neurological disorder, systemic disease, previous hospitalisation for shoulder pain and proximal humerus fractures.The primary outcome is the Western Ontario Shoulder Index at 6 months postoperatively. Secondary outcomes include incidence of recurrent dislocations, RTS and return-to-work rates, Tampa Scale of Kinesiophobia for Shoulder Instability, subjective shoulder value and visual analogue score for pain at 6 months postoperatively as well as the Shoulder Instability Return to Sport after Injury scale at 4.5 months postoperatively.Ethics and disseminationThis study was approved by the French Committee of Person Protection West I. The national registration number is 2023-A02057-38. The study has been registered at Clinicaltrials.gov with trial registration number NCT06154889. Patients are not financially compensated for participation and are allowed to withdraw from the study at any time without any preconditions. The final results of the study will be submitted for publication in a peer-reviewed journal and an abstract of the study will be submitted to international scientific meetings by the end of 2026. Data will be made available by the corresponding author on reasonable request.Registration detailsThe study has been registered at Clinicaltrials.gov with trial registration number NCT06154889. The trial sponsor is Vivalto Santé.Trial registration numberNCT06154889.

Background and purposeThe 2 most common surgical approaches in hemiarthroplasty for hip fracture treatment are the posterolateral and the direct lateral approach. We aimed to estimate the relative cost-effectiveness of these approaches.MethodsWe conducted an economic evaluation alongside a randomized controlled superiority trial for 6 months. The trial included 555 patients over 18 years of age with an acute femoral neck fracture. The effectiveness outcome used was quality-adjusted life years (QALYs), assessed using the EQ-5D-5L. Costs were measured through self-reported questionnaires administered at baseline, after 3 months, and after 6 months. We dealt with missing data through multiple imputation and analyzed the imputed datasets by comparing group means in costs and QALYs. A secondary analysis included adjustment for baseline imbalances through linear regression.ResultsThe estimated average treatment effect on the QALYs was 0.02 (95% confidence interval [CI] –0.006 to 0.046). From the healthcare and societal perspective, we found a non-significant average treatment effect on costs of 1,508 (CI –1,744 to 4,760) and 1,583 (CI –1,972 to 5,137), respectively. The probability of cost-effectiveness was 10% at a willingness-to-pay of zero, and then slowly increased to around 50% for higher willingness-to-pay values.ConclusionWe found no conclusive evidence of any differences between the surgical approaches with respect to costs, QALYs, and cost-effectiveness. We therefore suggest that, from an economic viewpoint, the 2 surgical approaches should be treated as interchangeable.

Berendsen, Remco R., Dirk C.A.A. de Vries, Alea Steger, Nadine Herold, Feico J.J. Halbertsma, Adriaan F. Norbart, Hannes Gatterer, and Bengt Kayser. Lack of altitude medicine knowledge among mountaineers in the Italian Alps. High Alt Med Biol. 26:361-373, 2025. Introduction: In 2022, expert consensus defined a set of minimum altitude medicine knowledge statements for laypersons traveling to high altitudes (STAK: strengthening altitude knowledge). We used these statements to assess knowledge among mountaineers in the Italian Alps. Methods: Mountaineers in a hut (3,647 m) completed an online STAK-based questionnaire, also indicating their confidence after each answer. A score of ≥19/28 was used as a statistical threshold, exceeding chance alone. Logistic regression assessed the link between confidence and correctness; multivariate regression explored demographic, educational, and behavioral predictors of achieving an above-threshold score. Results: Of 576 participants, 412 (72%) were included in the final analysis and 115 (28%) scored ≥19. Among them, 59% of medical professionals, 36% of mountain guides, and 23% of general participants reached the threshold; the medical professionals scored significantly higher than the general participants (p < 0.001). Both being a mountain guide (odds ratios [OR]: 2.3, 95% confidence intervals [CI]: 1.0-5.0, p < 0.05) and being a medical professional (OR: 4.5, 95% CI: 2.1-10.0, p < 0.001) were associated with higher scores. Conclusion: Using STAK as a benchmark, we found a substantial lack of altitude medicine knowledge in mountaineers, even among guides and medical professionals. These findings suggest a potential for targeted educational interventions.

IntroductionInguinal hernia repair is one of the most frequently performed operations in the paediatric population and can be performed according to two approaches: open or laparoscopic. At present, decisive evidence about the best treatment strategy is lacking and consequently, there is an ongoing debate about the most (cost-)effective treatment for the paediatric inguinal hernia. The aim of the Hernia Endoscopic oR opeN repair In chIldren Analysis—trial (HERNIIA2-trial) is to estimate the (cost-)effectiveness of the laparoscopic percutaneous internal ring suturing (PIRS) technique compared with open repair in children aged 0–16 years with a primary unilateral inguinal hernia.Methods and analysisA national multicentre randomised controlled trial will be performed including 464 children aged 0–16 years with a primary unilateral inguinal hernia. Patients will be randomised between the open or PIRS technique. The primary outcome is the number of reoperations within 2 years after primary surgery. Secondary outcome measures are: operative and postoperative complications, total duration of surgery, postoperative pain, length of admission, time to normal daily activities, cosmetic appearance of the scar, social and healthcare costs and health-related quality of life. Furthermore, cost-effectiveness will be assessed from a societal and healthcare perspective.Ethics and disseminationThe protocol was approved by the ethics committee of the Amsterdam University Medical Hospital. Informed consent will be obtained by parents and, if possible, according to age, by patient. The study will be conducted according to the principles of the Declaration of Helsinki (2013) and in accordance with the Medical Research Involving Human Subjects Act (WMO) and Good Clinical Practice. Study findings will be disseminated through scientific publications, conferences and patient-friendly materials. The national study network of participating centres will facilitate rapid dissemination and implementation within the Netherlands and potentially abroad.Trial registration numberClinicalTrials.gov PRS (ID NCT06451432).

ABSTRACTThis prospective study assessed the prevalence, type, and consequences of persistent symptoms following a nonhospitalized SARS‐CoV‐2 infection by comparing infected and noninfected children and adults of Dutch households. Two comparable prospective household studies were conducted during two pandemic phases. At baseline, all household members were tested for SARS‐CoV‐2 with 10 consecutive saliva samples during a 6‐week period using RT‐PCR. Questionnaires assessing persistent symptoms, health‐related quality of life (HRQoL), anxiety, and depressive symptoms were collected at 6 and 12 months. Of the 297 included participants (median age 34 years, IQR 12–48), 201 (67.7%) tested positive for SARS‐CoV‐2. At 6 months, only one child reported persistent symptoms. SARS‐CoV‐2‐infected adults (> 18 years) reported more pulmonary symptoms (15.2% vs. 3.4%, p = 0.023), and tended to report more fatigue (12.8% vs. 3.4%, p = 0.061) and exertion‐related symptoms (8.8% vs. 1.7%, p = 0.107) compared to the negative adults. Adult participants with persistent symptoms reported decreased HRQoL and increased anxiety and depressive symptoms. This study found that SARS‐CoV‐2‐positive adults tended to have higher prevalence of respiratory symptoms, fatigue, and exertion‐related symptoms 6 months after SARS‐CoV‐2 infection, whereas children rarely reported persistent symptoms. Persistent symptoms were associated with a reduced HRQoL and increased anxiety and depression.